Abstract 6799: A porous silicon particle based particulate anti-cancer vaccine for immunotherapy
Authors: Junhua Mai, Yongbin Liu, Dongfang Yu, Haifa Shen
Journal: Cancer Research (2023)

Abstract Background: Anti-cancer vaccine is a widely-studied strategy that activates innate and adaptive host immunity via its adjuvant components and tumor antigens against cancer. Unfortunately, its response rate in clinical trials was not promising. On the vaccine part, sufficient stimulation of strong and long-lasting local and systemic immunity and efficient promotion of intratumoral infiltration of cytotoxic T lymphocytes are among the critical issues determining the therapeutic efficacy of cancer vaccines in addition to the innate features of tumor. Our project aims to develop a porous silicon particle based particulate vaccine against cancer, and investigate the therapeutic mechanism and combinational effects with current first-line strategies. Method: We first screened the combinations of ligands of Toll-like receptors (TLRs) expressing on antigen presenting cells (APCs) and selected the most powerful combo for immune stimulation. We then loaded the identified adjuvants in addition to antigen peptides to produce vaccine particles. Stimulation and licensing of APCs were tested in vitro, and its therapeutic efficacies were evaluated on multiple orthotopic and systemic metastasis cancer murine models of breast and colon cancers. Furthermore, we investigated the vaccine’s synergistic effects and impacts on tumor microenviroment (TME) with an immunogenic chemotherapeutic oxaliplatin on a CT26 colon cancer model. Result: According to the adjuvant screening assays, we identified a capable combination of CpG1826 (CpG) and 2’3’-cGAMP (cGAMP), which extensively stimulated the activation, maturation and type-I interferon secretion of APCs. A µGCVax formulation composed by these two adjuvants and antigen peptides was then applied on primary and metastatic HER2+ breast cancer TUBO bearing mice. µGCVax potently promoted the activation and lymph node migration of CD8+ and CD103+ dendritic cells in vivo. Distal metastatic tumor nodules in all different tissues vanished after two vaccinations. Functional cure of cancer and extension of animal survival were achieved. Moreover, oxaliplatin treatment on colon cancer caused immunogenic cell death and generated an immune favorable TME in a subcutaneous CT26 colon cancer model. The combination of µGCVax with the oxaliplatin effectively blocked the progression of large tumor mass. We finally revealed that the reprogramming of TME and the promotion of efficacy were mostly achieved from diminishing myeloid-derived suppressor cells (MDSCs) in tumor. Conclusion: µGCVax is an effective and board-spectrum formulation for cancer immunotherapy. It effectively induces APC activation and licensing, and stimulates the innate and adaptive immunity against multiple cancers. The combination with oxaliplatin further promotes the therapeutic efficacy of µGCVax by decreasing tumor MDSCs. Citation Format: Junhua Mai, Yongbin Liu, Dongfang Yu, Haifa Shen. A porous silicon particle based particulate anti-cancer vaccine for immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6799.